Relative Risk Of Febrile Neutropenia Research Articles

Cost-effectiveness analysis of granulocyte colony-stimulating factors for the prophylaxis of chemotherapy-induced febrile neutropenia in patients with breast cancer in Taiwan.

To examine the cost-effectiveness of using granulocyte colony-stimulating factor (G-CSF) for primary or secondary prophylaxis in patients with breast cancer from the perspective of Taiwan's National Health Insurance Administration. A Markov model was constructed to simulate the events that may occur during and after a high-risk chemotherapy treatment. Various G-CSF prophylaxis strategies and medications were compared in the model. Effectiveness data were derived from the literature and an analysis of the National Health Insurance Research Database (NHIRD). Cost data were obtained from a published NHIRD study, and health utility values were also obtained from the literature. Sensitivity analyses were performed to assess the uncertainty of the cost-effectiveness results. In the base-case analysis, primary prophylaxis with pegfilgrastim had an incremental cost-effectiveness ratio (ICER) of NT$269,683 per quality-adjusted life year (QALY) gained compared to primary prophylaxis with lenograstim. The ICER for primary prophylaxis with lenograstim versus no G-CSF prophylaxis was NT$61,995 per QALY gained. The results were most sensitive to variations in relative risk of febrile neutropenia (FN) for pegfilgrastim versus no G-CSF prophylaxis. Furthermore, in the probabilistic sensitivity analysis, at a willingness-to-pay threshold of one times Taiwan's gross domestic product per capita, the probability of being cost-effective was 88.1% for primary prophylaxis with pegfilgrastim. Our study suggests that primary prophylaxis with either short- or long-acting G-CSF could be considered cost-effective for FN prevention in breast cancer patients receiving high-risk regimens.

Prophylactic pegfilgrastim to prevent febrile neutropenia among patients receiving biweekly (Q2W) chemotherapy regimens: a systematic review of efficacy, effectiveness and safety

BackgroundPegfilgrastim, a long-acting granulocyte colony-stimulating factor (G-CSF), is commonly used to prevent febrile neutropenia (FN), a potentially life-threatening complication, following myelosuppressive chemotherapy. The FDA label for pegfilgrastim specifies that it should not be administered 14 days before or within 24 h of administration of myelosuppressive chemotherapy, precluding the use of pegfilgrastim in biweekly (Q2W) regimens. The National Comprehensive Cancer Network and the European Organisation for Research and Treatment of Cancer guidelines support the use of prophylactic pegfilgrastim in patients receiving Q2W regimens. The objective of this study was to systematically review evidence from randomized clinical trials (RCTs) and observational studies that describe the effectiveness and safety of prophylactic pegfilgrastim in preventing FN among patients receiving Q2W regimens.MethodsAn Ovid MEDLINE, Embase, and Cochrane Library literature search was conducted to evaluate the evidence regarding efficacy, effectiveness, and safety of prophylactic pegfilgrastim versus no prophylactic pegfilgrastim or prophylaxis with other G-CSF in patients who were receiving Q2W chemotherapy regimens with high (> 20%) or intermediate (10–20%) risk of FN for a non-myeloid malignancy. Studies that addressed absolute or relative risk of FN, grade 1–4 neutropenia, all-cause or any hospitalization, dose delays or dose reductions, adverse events, or mortality were included. Studies where the comparator was a Q3W chemotherapy regimen with primary prophylactic pegfilgrastim were also included.ResultsThe initial literature search identified 2258 publications. Thirteen publications met the eligibility criteria, including eight retrospective, one prospective, one phase 1 dose escalation study, and three RCTs. In nine of the 13 studies reporting incidence of FN, and in seven of the nine studies reporting incidence of neutropenia, administration of prophylactic pegfilgrastim in patients receiving Q2W regimens resulted in decreased or comparable rates of FN or neutropenia compared with patients receiving filgrastim, no G-CSF, lipefilgrastim or pegfilgrastim in Q3W regimens. In six of the nine studies reporting safety data, lower or comparable safety profiles were observed between pegfilgrastim and comparators.ConclusionsIn a variety of non-myeloid malignancies, administration of prophylactic pegfilgrastim was efficacious in reducing the risk of FN in patients receiving high- or intermediate-risk Q2W regimens, with an acceptable safety profile.Trial registrationPROSPERO registration no: CRD42019155572.

Association of risk of febrile neutropenia (FN) with docetaxel in prostate cancer (PC) patients: A meta-analysis of published phase II-III trials.

e21683 Background: Reported rates of FN with docetaxel (DTX) in PC patients are variable. This creates uncertainty regard the use of granulocyte colony-stimulating factor primary prophylaxis (G-CSF) in this setting. We conducted a meta-analysis of randomized clinical trials to determine the relative risk (RR) of FN in patients receiving DTX. Methods: To perform this analysis we systematically searched in PUBMED and MEDLINE database the following terms: “DTX”, “randomized clinical trial” and “prostate cancer” only for articles published between January 1996 and August 2016. Phase II-III clinical studies comparing DTX to non-DTX control arms (best supportive care [BSC] including non-cytotoxic therapy or mitoxantrone) for PC were included. The meta-analyses were performed by computing RRs with 95% confidence intervals (CI) using fixed-effects model with the Mantel-Haenszel method. Results: Seven studies (N = 5088 patients) were included. The global incidence of FN in patients treated with DTX was 10.7%. The RR of FN was higher in patients receiving DTX compared to patients did not receive DTX (RR 16.8 [95% CI 10.7; 26.4] p < 0.0001). 6.6% of patients with metastatic castration resistant prostate cancer (CRPC) treated with DTX developed FN, the RR of FN with DTX compared to mitoxantrone was 28.6 (95% CI 5.6; 145.1). 12.4% of patients with hormone-sensitive prostate cancer (HSPC) treated with DTX developed FN, the RR of FN was 15.3 (95% CI 9.6; 24.6) compared to BSC. There was no statistically significant differences in the rate of FN according to the hormone sensitivity (HSPC vs CRPC) (p = 0.7). In most studies the use of G-CSF was at the discretion of the investigator. Conclusions: This meta-analysis shows that DTX is associated with a significant increase in the relative risk of FN in patients with PC. The effectiveness of primary prophylactic G-CSF in this setting has not been fully established. The incidence reported here does not meet the threshold recommended by ESMO and ASCO guidelines for the use of prophylactic G-CSF. Special attention should be given to high risk groups for FN, including elderly patients and those with bone marrow involvement or previous radiotherapy/chemotherapy.

S-1-Based Regimens for Locally Advanced/Metastatic Non-Small-Cell Lung Cancer: A Meta-Analysis

We performed a meta-analysis of S-1-containing regimens versus control in the management of locally advanced/metastatic non-small-cell lung cancer. Eligible studies included randomized studies evaluating S-1-containing regimens in the settings of locally advanced, first-line metastatic or second-line metastatic non-small-cell lung cancer. Pooled odds ratio for overall response rate was 1.09 (95% CI: 0.85-1.38; p = 0.2), the pooled hazard ratio for progression-free survival was 0.98 (95% CI: 0.88-1.09; p = 0.69) and the pooled hazard ratio for overall survival was 0.98 (95% CI: 0.88-1.10; p = 0.75) for S-1-based regimens versus control. Moreover, the relative risk of febrile neutropenia was 0.34 (95% CI: 0.20-0.59; p = 0.0001). Our meta-analysis has demonstrated that S-1-based regimens are associated with similar efficacy outcomes and better hematological tolerability.

Importance of Risk Factors for Febrile Neutropenia Among Patients Receiving Chemotherapy Regimens Not Classified as High-Risk in Guidelines for Myeloid Growth Factor Use.

Clinical practice guidelines recommend prophylaxis in patients with cancer receiving a colony-stimulating factor (CSF) when the risk of febrile neutropenia (FN) is high (>20%). For patients receiving chemotherapy regimens not documented as high-risk, the decision regarding CSF prophylaxis use can be challenging, because some patients may be at high risk based on a combination of the regimen and individual risk factors. A retrospective cohort design and US private health care claims data were used. Study subjects received chemotherapy regimens classified as "low" or "intermediate," or unclassified, in terms of FN risk, and were stratified by cancer and regimen. For each subject, the first chemotherapy course, and each cycle and FN episode within the course, were identified. FN incidence proportions were estimated by the presence and number of risk factors and chronic comorbidities. Across the 17 tumor/regimen combinations considered (n=160,304 in total), 74% to 98% of patients had 1 or more risk factor for FN and 41% to 89% had 2 or more. Among patients with 1 or more risk factor, FN incidence ranged from 7.2% to 29.0% across regimens, and the relative risk of FN (vs those without risk factors) ranged from 1.1 (95% CI, 0.8-1.3) to 2.2 (95% CI, 1.5-3.0). FN incidence increased in a graded and monotonic fashion with the number of risk factors and comorbidities. In this retrospective evaluation of patients with cancer receiving chemotherapy regimens not classified as high-risk for FN in US clinical practice, most patients had 1 or more FN risk factor and many had 2 or more. FN incidence was found to be elevated in these patients, especially those with multiple risk factors.

Cost-effectiveness of prophylaxis treatment strategies for febrile neutropenia in patients with recurrent ovarian cancer

ObjectiveEvaluate the cost-effectiveness of primary prophylaxis (PP) or secondary prophylaxis (SP) with pegfilgrastim, filgrastim (6-day and 11-day), or no prophylaxis to reduce the risk of febrile neutropenia (FN) in patients with recurrent ovarian cancer receiving docetaxel or topotecan. MethodsA Markov model was used to evaluate the cost-effectiveness of PP vs SP from a US payer perspective. Model inputs, including the efficacy of each strategy (relative risk of FN with prophylaxis compared to no prophylaxis) and mortality, costs, and utility values were estimated from public sources and peer-reviewed publications. Incremental cost-effectiveness was evaluated in terms of net cost per FN event avoided, incremental cost per life-year saved (LYS), and incremental cost per quality-adjusted life-year (QALY) gained over a lifetime horizon. Deterministic and probabilistic sensitivity analyses (DSA and PSA) were conducted. ResultsFor patients receiving docetaxel, the incremental cost-effectiveness ratio (ICER) for PP vs SP with pegfilgrastim was $7900 per QALY gained, and PP with pegfilgrastim dominated all other comparators. For patients receiving topotecan, PP with pegfilgrastim dominated all comparators. Model results were most sensitive to baseline FN risk. PP vs SP with pegfilgrastim was cost effective in 68% and 83% of simulations for docetaxel and in >99% of simulations for topotecan at willingness-to-pay thresholds of $50,000 and $100,000 per QALY. ConclusionsPP with pegfilgrastim should be considered cost effective compared to other prophylaxis strategies in patients with recurrent ovarian cancer receiving docetaxel or topotecan with a high risk of FN.

Cost-effectiveness of pegfilgrastim versus 6-day filgrastim primary prophylaxis in patients with non-Hodgkin's lymphoma receiving CHOP-21 in United States

ABSTRACTObjectives: Prophylaxis with granulocyte-colony stimulating factor (G-CSF) reduces the risk of febrile neutropenia (FN) in patients receiving myelosuppressive chemotherapy. Randomized clinical trials have shown that pegfilgrastim, a 2nd-generation G-CSF, is at least as effective as the 1st-generation G-CSF filgrastim. In the meta-analysis of trials pegfilgrastim performed better than filgrastim with respect to FN risk. The incremental cost-effectiveness of primary prophylaxis (starting in cycle 1 and continuing in subsequent cycles of chemotherapy) with pegfilgrastim versus filgrastim used for 6 days (as is often used in clinical practice) was estimated in patients with aggressive non-Hodgkin's lymphoma (NHL) receiving myelosuppressive chemotherapy in the United States.Methods: A decision-analytic model was constructed from a health insurer's perspective with a life-time study horizon. The model considered direct medical costs and outcomes related to reduced FN and potential survival benefits due to reduced FN-related mortality. Inputs for the model were obtained from the medical literature. Sensitivity analyses were conducted across plausible ranges in parameter values.Results: The incremental cost-effectiveness (ICER) of pegfilgrastim versus 6-day filgrastim primary prophylaxis was $2167/FN episode avoided. Adding survival benefit from avoiding FN mortality yielded an ICER of $5532/LY gained or $6190/QALY gained. When the potential benefit of optimized chemotherapy was included, the ICER was $1494/LY gained or $1677/QALY gained. The most influential factors included cost of pegfilgrastim, relative risk of FN between pegfilgrastim and filgrastim, FN case-fatality rate, cost of filgrastim and baseline FN risk.Conclusions: Pegfilgrastim is cost-effective in primary prophylaxis of FN compared to 6 days per cycle of filgrastim, in patients with NHL receiving myelosuppressive chemotherapy (e.g., cyclophosphamide + doxorubicin + vincristine + prednisolone [CHOP-21]) chemotherapy. Study limitations included lack of direct evidence linking G-CSF use with a reduction in FN-related mortality and limited data that show a relationship between relative dose intensity (RDI) and cancer-specific patient survival.